The invention relates to a process for the production of betaines of formulaR3N+-Q-COO−  (I),wherein R is C1-4 alkyl and Q is C1-4 alkanediyl, optionally substituted with hydroxy. More specifically, the invention relates to a process for the production of carnitine. Carnitine (I, R═CH3, Q=—CH2—CHOH—CH2—), and in particular the L-enantiomer of carnitine, is a vitamin-like substance that plays an important role in fatty acid metabolism.
L-Carnitine can be produced by biotechnological or chemical processes. U.S. Pat. No. 4,708,936 and U.S. Pat. No. 5,187,093 describe the production of L-carnitine by microbial biotransformation of butyro-betaine (I, R═CH3, Q=—(CH2)3—). Several chemical processes involve the optical resolution of DL-carnitine. Other chemical processes are based on the asymmetric hydrogenation of γ-tri-methylammonioacetoacetates to L-carnitine esters (EP 0 375 417 A2), or the asymmetric hydrogenation of γ-chloroacetoacetates to L-γ-chloro-β-hydroxybutyrates which, in a subsequent step, are reacted with trimethylamine to the corresponding carnitine esters (U.S. Pat. No. 4,895,979). In both cases the L-carnitine esters are subjected to acid hydrolysis to yield a salt of L-carnitine (e.g. L-carnitine hydrochloride) which in turn has to be converted (e.g. by ion exchange) into the free betaine form of L-carnitine. These processes are relatively tedious and result in the formation of large amounts of salt byproducts which have to be disposed of.
JP-A-60-161952 discloses the production of carnitine from γ-chloro-β-hydroxybutyric acid or the methyl or propyl ester of γ-chloro-β-hydroxybutyric acid and trimethylamine in the presence of an alkali hydroxide. The reaction vessel is charged with the acid or ester and trimethylamine and alkali hydroxide are added either consecutively or as a mixture. The reported yields of carnitine are between 44% and 75%.
It is an object of the present invention to provide an improved chemical process for the production of L-carnitine and related betaines which gives the desired products in high yield and does not require a separate hydrolysis step.
According to the invention, this object has been achieved by the process of claim 1.